High-throughput screening has been used to successfully detect single protein changes or other simple changes in microorganisms. Microorganisms that produce a particular metabolite or are high-producers of a particular metabolite, such as metabolically engineered microorganisms, tend to exhibit combinatorial optimization involving multi-gene pathways and interacting cellular networks, which simultaneously perturb multiple cellular pathways to achieve an increase in a metabolite. Screening for metabolites resulting in such complex changes is not compatible with existing high-throughput screening technologies. Instead, microorganisms producing a particular metabolite tend to be screened using expensive, slow, or limited-target methods, such as small molecule metabolite detection via gas/liquid chromatography, fluorescence-activated cell sorting, or even growth selection on agar plates. Other screening methods have relied on complex binding and signal-transduction functions, which have not proven readily adaptable to a variety of targets and contexts.
As a result, the number of microorganisms available to produce useful metabolites is limited. Yet, such organisms may be identified from samples and metabolically engineered microorganisms may be produced quite readily using any of numerous different technologies that are able to produce large strain libraries, often each including more than 106 different strains. If these various microorganisms could be screened in a high-throughput assay for a given metabolite, high-producing strains as well as high-producing culture conditions could be rapidly identified, the costs of such products could be lowered and availability increased. Furthermore, new metabolites with desirable functions may be identified.